Effect of Cholesterol on the Properties of Phospholipid Membranes,
4. Interatomic Voids.
The properties of the interatomic voids present in fully hydrated dimyristoylphosphatidylcholine (DMPC)-
cholesterol mixed membranes of different compositions are analyzed in detail using a generalized variant of
the Voronoi-Delaunay method on the basis of computer simulation results. The systems investigated are
chosen from both sides of the DMPC-cholesterol miscibility gap; the pure DMPC bilayer has also been
included in the analysis as a reference system. The results obtained show that the empty space is organized
in a more compact way, forming larger voids in the presence than in the absence of cholesterol. The voids
located in the region of the rigid cholesterol rings become, on average, less spherical, oriented more parallel
with the membrane normal axis with increasing cholesterol concentration, whereas an opposite effect of
cholesterol is observed in the middle of the membrane among the chain terminal methyl groups. In general,
the preferential orientation of the voids is found to strongly correlate with that of the molecules in the
hydrocarbon phase of the membranes. The membranes are found to contain rather large voids, the volume of
which can be an order of magnitude larger than the largest spherical cavities present in the systems. These
voids are elongated or branching channels rather than big empty holes. The voids located among the DMPC
and cholesterol molecules are lying preferably parallel with the membrane normal axis. The existence of
such empty channels can be of great importance in the cross-membrane permeation of small, uncharged
penetrants, in particular, of polar molecules.